a. Field of the Invention
The present invention relates to so-called fluorescence references which are useful for checking the operation of fluorescence measuring apparatus used in applications such as medical diagnostic technology.
b. Description of the Related Art
Fluorescent materials are used as detection media in areas such as analytical, medical and biological testing or characterization. In fluorescence, a material absorbs light energy and subsequently loses some of that energy by emitting light at a characteristic, and often different, wavelength. In general, detection techniques are structured around a specific reaction or interaction that changes the intensity of a fluorescent signal in relation to the presence of a material of interest.
One exemplary application of fluorescence is a test procedure for approximating the concentration of a given antibody in a patient's body fluid using fluorescent-tagged antigens which are specific to the antibody. A sample is prepared which contains the patient's body fluid and fluorescent-tagged antigens. When light of a suitable wavelength is applied to the sample, the fluorescent material will absorb this light and emit characteristic fluorescence at longer wavelengths. If antibodies are present, they will bind with the tagged antigens. The interaction is designed to change the fluorescent signal proportionally and, depending on the type of interaction, the change will be either an increase or a decrease in signal. Therefore, observing the change in the fluorescence gives a direct correspondence to the concentration of the antibodies in the fluid. Signal intensity graph 5 of FIG. 1 illustrates the situation when the signal is increased.
As is well known, fluorescence references are used to check the accuracy of fluorescence-measuring apparatus or instruments.
Common references for fluorescence measurements are organic dyes, which are dissolved to specific concentrations in solvents. The organic dye solution is contained, for example, in cuvettes or dripped into the wells of a test card. The available solvent-dispersed organic dye references do not maintain stable fluorescence values over time and, being liquid, are relatively difficult to shape, handle and store.
As described in the following patents, non-liquid fluorescent materials have been used in control applications. For example, SU patent 1,751,825 describes the combination of a luminophor layer with aluminum and metal oxide absorption layers used in the production of cathode ray tubes. The absorption layer is used to control gas transfer rather than correct light amplitude. Two patents, U.S. Pat. No. 5,021,327 and U.S. Pat. No. 4,865,944, describe different designs incorporating filters and/or fluorescent layers to improve and control radiographic film exposure. This is a significantly different application from fluorescence referencing, and involves X-ray conversion to visible light rather than UV-visible-IR control. U.S. Pat. Nos. 4,975,619 and 4,921,727 describe coatings and the use of coatings on phosphor particles themselves to control triboelectricity rather than optical properties. In their most relevant aspects, the above patents relate directly to: (a) the production of cathode ray tubes (CRTs) or phosphor screens, rather than fluorescence references; (b) the control of physical properties for easier handling, rather than spectral regulation; and (c) conversion of energy for more efficient and uniform exposure of radiographic silver halide films, rather than referenced sources of fluorescence.